Liposomes for Drug Delivery
Liposomes are microscopic spheres which were developed as drug delivery vehicles/systems in the 1980s. The first liposome-based pharmaceuticals were approved for commercial use in the 1990s.
Liposomes have three distinct compartments that can be used to carry various compounds such as drugs: The interior aqueous compartment; the hydrophobic bilayer; and the polar inter-phase of the inner and outer leaflet. Depending on the chemical nature of the compound to be encapsulated it will be localised to either of the compartments.
Currently, there are several parenteral liposome-drug formulations available on the market. Water soluble drugs tend to be localised in the aqueous compartment of liposomes, and examples of drugs encapsulated in liposome's are, e.g. doxorubicin (Doxil), doxorubicin (Myocet) and daunorubicin (DaunoXone). Examples of drugs intercalated in the liposome membrane are, e.g. amphotericin B (AmBisome), amphotericin (Albelcet B), benzoporphyrin (Visudyne) and muramyltripeptide-phosphatidylethanolamine (Junovan).
Liposomes are considered a promising drug delivery system since they passively target tumor tissue by using the pathophysiological characteristics of solid tumors such as hyperplasia and increased vascular permeability but also a defect in lymphatic drainage. These features facilitate extravasation of nanoparticles and the liposomes can be retained in the tissue for longer time due to the enhanced permeability and retention effect (EPR).
The property of liposomes as drug delivery vehicles is crucially dependent on their surface charge, permeability, solubility, stability etc. which is significantly influenced by the lipids comprised in the liposome composition. In addition, the drug to be encapsulated in the liposome may need further requirements to be considered in preparing a stable liposome formulation.
Considerations regarding safety and drug efficacy require that liposome formulations maintain their properties, i.e. remain stable, from the time of preparation until administration.
Furthermore, it is desirable that such formulations are intact during the transport in the treated subject until they reach the target site where the drug is specifically released.
Various targeting strategies for liposomes have been described, e.g. conjugation to cell specific ligands such as antibodies.
sPLA2 Hydrolysable Liposomes
Another approach has been suggested based upon elevated levels of secretory phospholipase A2 (sPLA2) in cancerous tissue and also at sites of inflammation. The basic idea is that liposomes can be prepared which are hydrolysable by sPLA2 and that hydrolysis by sPLA2 leads to release of the drug encapsulated within the liposome. Moreover, the products of sPLA2 hydrolysis, a lysolipid and a fatty acid act as permeabilizers of cell membranes leading to increased cell uptake of the drug. Since sPLA2 levels are elevated in cancerous tissues and at sites of inflammation, sPLA2 activated liposomes may be used to preferentially deliver encapsulated drugs to such sites.
Storage Stability of sPLA2 Hydrolysable Liposomes
sPLA2 hydrolysable liposomes pose special challenges with regards to storage stability. These challenges are based in the particular lipid composition necessary for effective sPLA2 hydrolysis.
In general, many parameters influence storage stability, and it is difficult to predict the consequences of altering buffer composition on storage stability as this affects not only the osmolarity, but also the membrane stability.